OBJECTIVETo evaluate the relationship of hypoxia-inducible factor (HIF)-1alpha expression with chemotherapy response in gastric cancer and its clinical outcome.

METHODSLeucovorin (CF) and 5-fluorouracil (5-FU) in combination with oxaliplatin (L-OHP) were used in 52 patients with gastric carcinoma (GC) at advanced stage. CF 200 mg/m(2) was intravenous drop for 2 h at day 1 and day 14. 5-FU 1500 mg/m(2) was continuously intravenous drop for 46 h at day 1 and day 14. L-OHP 85 mg/m(2) was intravenous drop for 2 h at day 1 and day 14. Four-week was one cycle. All the patients received 4 cycles of chemotherapy at least. Chemotherapy response and clinical outcome were evaluated. Immunohistochemistry was used to examine the protein expressions of HIF-1alpha, P-gp and MRP4 by tissue microarray in GC. Twenty-seven normal gastric tissue samples were used as control group.

RESULTSThe positive expression rates of HIF-lalpha, P-gp and MRP4 in tumor samples were 53.9%, 51.9% and 57.7% respectively, which were significantly higher than those in normal gastric tissues (0, 18.5% and 14.8% respectively) (P<0.05). In cases with positive expression of HIF-lalpha, the response rate was 14.3%; whereas in cases with negative expression of HIF-1alpha, the response rate was 50.0%. There was significant difference between two groups (P<0.05). In patients of HIF-1alpha positive expression,the median progression-free survival time was 4.7 months,the median survival time was 8.8 months, and 1-year, 2-year survival rates were 37.5% and 21.5% respectively. In patients of HIF-1alpha negative expression, the median progression-free survival time was 8.4 months, the median survival time was l2.6 months, and 1-year, 2-year survival rates were 51.2% and 33.5% respectively. There were significant differences between two groups (P<0.05).

CONCLUSIONHIF-1alpha expression may be a useful indicator to predict the chemotherapy response and clinical outcome in gastric carcinoma.